Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
Abstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macroli...
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Wiley
2021-12-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.518 |
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| author | Stéphanie Pons Eden Arrii Marine Arnaud Maud Loiselle Juliette Ferry Manel Nouacer Julien Lion Shannon Cohen Nuala Mooney Lara Zafrani |
| author_facet | Stéphanie Pons Eden Arrii Marine Arnaud Maud Loiselle Juliette Ferry Manel Nouacer Julien Lion Shannon Cohen Nuala Mooney Lara Zafrani |
| author_sort | Stéphanie Pons |
| collection | DOAJ |
| description | Abstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. Methods Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T‐cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. Results ECs act as non‐professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA‐DR on septic‐stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin‐6 (IL‐6) and IL‐8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL‐6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T‐helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. Conclusion This study reports phenotypic and gene expression changes in septic‐stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co‐cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis. |
| format | Article |
| id | doaj-art-2d6405c662544f71bfa0f420c3450e13 |
| institution | Kabale University |
| issn | 2050-4527 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj-art-2d6405c662544f71bfa0f420c3450e132025-08-20T03:58:37ZengWileyImmunity, Inflammation and Disease2050-45272021-12-01941656166910.1002/iid3.518Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulationStéphanie Pons0Eden Arrii1Marine Arnaud2Maud Loiselle3Juliette Ferry4Manel Nouacer5Julien Lion6Shannon Cohen7Nuala Mooney8Lara Zafrani9Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceHuman Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Université de Paris Paris FranceAbstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. Methods Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T‐cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. Results ECs act as non‐professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA‐DR on septic‐stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin‐6 (IL‐6) and IL‐8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL‐6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T‐helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. Conclusion This study reports phenotypic and gene expression changes in septic‐stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co‐cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.https://doi.org/10.1002/iid3.518antibioticsendotheliumimmunoregulationseptic shockinflammation |
| spellingShingle | Stéphanie Pons Eden Arrii Marine Arnaud Maud Loiselle Juliette Ferry Manel Nouacer Julien Lion Shannon Cohen Nuala Mooney Lara Zafrani Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation Immunity, Inflammation and Disease antibiotics endothelium immunoregulation septic shock inflammation |
| title | Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation |
| title_full | Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation |
| title_fullStr | Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation |
| title_full_unstemmed | Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation |
| title_short | Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation |
| title_sort | immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation |
| topic | antibiotics endothelium immunoregulation septic shock inflammation |
| url | https://doi.org/10.1002/iid3.518 |
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